Oral microbial colonization involves a number of specific interactions between different bacteria. Viridans streptococci that initiate colonization of the tooth surface include strains with cell wall polysaccharides that are receptor molecules for the lectins of other oral bacteria. The cell wall polysaccharides of 23 streptococcal strains that are recognized by the Ga1/Ga1Nac lectins of Actinomyces naeslundii have been isolated and structurally characterized. These polysaccharides constitute five structural types each composed of a somewhat different hexa- or heptasaccharide repeating unit linked end-to-end by phosphodiester bonds or through ribitol phosphate. Lectin recognition of these molecules depends on a host-like disaccharide motif, either Ga1beta1-3Ga1NAc or Ga1NAcbeta1-3Ga1, present within each repeating unit. In contrast, the reactions of antipolysaccharide antibodies may involve structural features that are distinct from the immunorecessive host-like motifs. The closely related structures of different receptor polysaccharides and the specificities of antibody and lectin probes for these molecules, provide an attractive system for development of a molecular biological approach to engineer specific polysaccharides. This capability, which is the goal of this project, may contribute to the improved definition of the biological role of receptor polysaccharides in oral colonization and also to the development of new strategies for vaccine development. Current studies are focused on identification of the gene clusters for receptor polysaccharides. This involves the isolation and characterization of transposon mutants that exhibit altered reactivity with specific antipolysaccharide antibodies. Further molecular characterization is also underway to identify genes for specific glycosyl tranferases and related biosynthetic enzymes that are determinants of polysaccharide structure.